Increased circulating prostaglandins (PG's), lipids with potent effects on smooth muscle, have neen noted to be increased in several pulmonary diseases (e.g., cyctic fibrosis, pulmonary edema, shock lung, and asthma); however, the importance of circulating PG's in pulmonary disease is not known. Previous studies in our laboratory indicate that the bolus injections of prostaglandins F2alpha, E2 and D2, arachidonic acid and a stable analog of endoperoxide into the superior vena cava or the left ventricle or anesthetized, paralyzed, and artifically ventilated dogs produce marked changes in pulmonary mechanics and in pulmonary vascular pressures. These studies suggested that vagally mediated reflex bronchoconstriction or direct stimulation of large airway smooth muscle were not predominant mechanisms of prostaglandin action. The purpose of this proposal is to investigate further the mechanisms by which stable analogs of prostaglandins E2 and F2alpha and endoperoxide delivered by continuous infusions into the pulmonary and bronchial circulation produce changes in pulmonary function. In addition, our objective is to study the interaction of changes in the lung and pulmonary circulation that are produced by these agents. We will determine if the mechanisms that are responsible for the changes in lung function are 1) secondary to pulmonary vascular congestion, 2) secondary to pulmonary edema, 3) secondary to vagally mediated reflexes, or 4) due to direct stimulation of smooth muscle in the airways and lung parenchyma. Physiologic measurements will include resistance of the respiratory system (Rrs), static and dynamic compliance (Cstat and Cdyn), pressures in the pulmonary artery, left atrium, and aorta, lung volumes, pulmonary blood flow (PBF) and pulmonary blood volume (PBV), shunt fraction (Qs/Qt), wasted ventilation (VD/VT), diffusion capacity for carbon monoxide (DLCO) and pulmonary capillary blood volume (PCBV), Morphologic studies will include tantalum bronchography, semigross examinatons of frozen lung sections and wet to dry lung weight ratios. By studying the mechanisms by which these agent influence lung function and correlating physiologic and structural changes the role of the prostaglandin system in the pathophysiology of pulmonary disease may be better understood.